Long non coding RNAs: new players in acute myeloid leukemia
Accumulating evidences indicate that different long-non coding RNAs (lncRNAs) might
play a relevant role in tumorigenesis, with their expression and function already associated
to cancer development and progression. CCAAT/enhancer-binding protein-α (CEBPA) is a
critical regulator of myeloid differentiation whose inactivation contributes to the
development of acute myeloid leukemia (AML). Mutations in C/EBPα occur in around 10%
of AML cases, leading to the expression of a 30-kDa dominant negative isoform (C/EBPα-
p30). In this study, we have utilized a CEBPα inducible cellular system for identifying
lncRNAs that regulate proliferation and differentiation of AML cells. Among them, we
identified the oncogenic urothelial carcinoma associated 1 (UCA1) lncRNA as a novel
target of the C/EBPα-p30 and we demonstrate that UCA1 sustains proliferation of AML
cells by repressing the expression of the cell cycle regulator p27kip1. Notably, we also show
that UCA1 expression increases in cytogenetically normal AML cases carrying biallelic
CEBPA mutations. Thus, we identified, for the first time, an oncogenic lncRNA functioning
in concert with the dominant negative isoform of C/EBPα in AML.